Since Leland Clark first proposed a theoretical model wherein the enzyme electrode was used to measure glucose in 1962 (Ref 1: Clark, L. C.; Jr.; Lyons, C. Electrode systems for continuous monitoring in cardiovascular surgery. Ann. N. Y. Acad. Sci. 1962, 102, 29-45), researchers have never stopped the study on glucose sensor. The basic model by Clark comprises the following three elements: an oxygen electrode, an oxygen semi-permeable membrane and glucose enzyme, wherein the enzyme is immobilized on the electrode (also referred to as an enzyme electrode). The detection principle is to measure reduction of oxygen concentration in blood and then to calculate glucose concentration, i.e., glucose is oxidized to produce hydrogen peroxide under the action of glucose oxidase, thus consuming blood oxygen. Therefore, the glucose concentration can be obtained by calculating the concentration reduction of blood oxygen.
It was in 1975 that Clark's model was really and successfully converted into commodity as a Model 23A YSI Analyzer, which was a glucose analyzer produced by Yellow Springs Instrument Company. The analyzer is also a standard glucose analyzer which is still used in world now. This instrument can calculate the glucose concentration by measuring hydrogen peroxide (H2O2). The basic principle thereof is to measure glucose concentration based on change of blood oxygen concentration. All instruments, which are used for measuring blood glucose and developed based on Clark's model, are based on measurement of blood oxygen. The problem is that oxygen in the blood is very limited and in μM magnitude. Compared with blood glucose in mM magnitude, such a low concentration is minimal. Therefore, for all instruments based on Clark's glucose model, blood must be diluted to a level that is at least equivalent to the level of oxygen in liquid before detection. However, the additional dilution step is not only cumbersome and time-consuming but also to introduce systematic errors which lead to inaccurate measurement results.
Hence, there is an urgent need in the art to develop a new detection method which can be used easily and can obtain accurate measurement results as well as corresponding detection tools.